Total and Phosphorylated Tau-protein and Beta-Amyloid42 in Cerebrospinal Fluid in Dementias and Multiple Sclerosis

Czech version

Authors: M. Vališ ¹; R. Taláb ¹; C. Andrýs ² ; P. Štourač ³; J. Masopust ⁴; D. Kalnická ⁵; G. Waberžinek ¹
Authors‘ workplace: Neurologická klinika LF UK a FN Hradec Králové ¹; Ústav klinické imunologie a alergologie LF UK a FN Hradec Králové ²; Neurologická klinika LF MU a FN Brno ³; Psychiatrická klinika LF UK a FN Hradec Králové ⁴; Psychiatrická léčebna Havlíčkův Brod ⁵
Published in: Cesk Slov Neurol N 2008; 71/104(3): 329-335
Category: Short Communication

Overview

Introduction:
Differential diagnosis of dementias is often difficult, and for this reason research into biomarkers that can assist in the diagnostic process has lately become important. The current study focuses on the diagnostic value of beta-amyloid42 (Aß-42), overall tau protein and phosphorylated tau protein for the diagnosis of Alzheimer's disease (AD), Creutzfeldt-Jakob disease (CJD) and multiple sclerosis (MS).

Methods:
18 patients diagnosed as having AD according to NINCDS-ADRDA criteria, 16 patients with isolated clinical syndrome suspected of MS (7 of them fulfilling McDonald's criteria) and 3 patients with CJD (WHO criteria) were included into the study together with a cognitive intact control group consisting of 38 individuals. A curve analysis for receiver operating characteristics (ROCs) was calculated to define the cut off concentrations for the biomarkers and the maximum sensitivity and specificity for the given group. Correlation was used in the final analysis.

Results:
In patients diagnosed with AD there was significant decrease of beta-amyloid42 level (616.5 pg/ml, p < 0.0001) and increase of tau protein level (451 pg/ml, p = 0.0003) compared to control group. In CJD there was marked elevation of tau protein level and increased total tau versus phosphorylated tau protein ratio in comparison with the AD group as well as the control group. No significant changes in biomarker levels were found for patients with MS.

Conclusion:
Our results are in line with the current literature on the value of the three biomarkers mentioned above in the differential diagnosis of AD and CJD. We have not found any such evidence in relation to MS.

Key words:
Alzheimer's disease – Creutzfeldt-Jakob disease – multiple sclerosis – beta-amyloid42 – total tau-protein – phosphorylated tau-protein

Sources

1. Bibl M, Mollenhauer B, Esselmann H, Lewczuk P, Klafki H-W, Sparbier K et al. CSF amyloid-ß-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia. Brain 2006; 129(Pt 5): 1177–1178.

2. Kapaki E, Paraskevas GP, Zalonis I, Zournas C. CSF tau-protein and ß-amyloid (1–42) in Alzheimer's disease diagnosis: discriminatiom from normal ageing and other dementias in the Greek population. Eur J Neurol 2003; 10(2): 119–128.

3. Friedland RP. Epidemiology, education and ecology of Alzheimer's disease. Neurology 1993; 43(2): 246–249.

4. Breteler MM, van Harskamp F, Claus JJ, van der Cammen TJ, Grobbee DE, Hofman A et al. Prevalence of Alzheimer’s disease and vascular dementia: association with education. The Rotterdam study. BMJ 1995; 310(6985): 970–973.

5. Wolfe MS. Therapeutic strategies for Alzheimer’s disease. Nat Rev Drug Discov 2002; 1(11): 859–866.

6. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984; 34(7): 939–944.

7. Small DH, McLean CA. Alzheimer's disease and the amyloid beta protein: What is the role of amyloid? J Neurochem 1999; 73(2): 43–449.

8. Hort J, Glosová l, Vyhnálek M, Bojar M, Škoda D, Hladíková M. Tau-protein a beta amyloid v likvoru u Alzheimerovy choroby. Cesk Slov Neurol N 2007; 70/103(1): 30–36.

9. Kapaki E, Kilidireas K, Paraskevas GP, Michalopoulou M, Patsouris E. Highly increased CSF tau-protein and decreased betaamyloid (1-42) in sporadic CJD: a discrimination from Alzheimer’s disease? J Neurol Neurosurg Psychiatry 2001; 71(3): 401–403.

10. Ledesma M, Medina M, Avila J. The invitro formation of recombinant tau polymer effect of phosphorylation and glycation. Mol Chem Neuropathol 1996; 27(3): 249–258.

11. Parnetti L, Lanari A, Amici S, Gallai V, Vanmechelen E, Hulstaert F. CSF phosphorylated tau is a possible marker for discriminating

Alzheimer’s disease from dementia with Lewy bodies. Phospho-Tau International Study group. Neurol Sci 2001; 22(1): 77–78.

12. Zeider M, Gibbs C, Meslin F. WHO manual for strengthening diagnosis and surveillance of Creutzfeldt-Jakob disease. World Health Organization 1998; 7–8: 47–51.

13. Hainfellner JA, Wanschitz J, Jellinger K, Liberski PP, Gullotta F, Budka H. Coexistence of Alzheimer-type neuropathology in Creutzfeldt-Jakob disease. Acta Neuropathol 1998; 96(2): 116–122.

14. McDonald WI, Compston A, Edan G, Goodkin D, Hartung H-P, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50(1): 121–127.

15. Luque FA, Jaffe SL. Cerebrospinal fluid analysis in multiple sclerosis. Int Rev Neurobiol 2007; 79: 341–356.

16. Brettschneider J, Maier M, Arda S, Claus A, Sussmuth SD, Kassubek J et al. Tau-protein level in cerebrospinal fluid is increased in patients with early multiple sclerosis. Mult Scler 2005; 11: 261–265.

17. Guimares I, Cardoso MI, Sá MJ. Tauprotein seems not to be a useful routine clinical marker of axonal damage in multiple sclerosis. Mult Scler 2006; 12(3): 354–356.

18. Kapaki E, Paraskevas GP, Michalopoulou M, Kilidireas K. Increased cerebrospinal fluid tau-protein in multiple sclerosis. Eur Neurol 2000; 43(4): 228–232.

19. Brettschneider J, Petzhold A, Junker A, Tumani H. Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis. Mult Scler 2006; 12(2): 143–148.

20. Munroe WA, Southwick PC, Chang L, Scharre DW, Echols CL, Fu PC et al. Tauprotein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer’s disease. Ann Clin Lab Sci 1995; 25(3): 207–217.

21. Tapiola T, Pirttila T, Mikkonen M, Mehta PD, Alafuzoff I, Koivisto K et al. Three-years follow-up of cerebrospinal fluid tau, beta-amyloid 42 and 40 concentrations in Alzheimer’s disease. Neurosci Lett 2000; 280: 119–122.

22. Pidrman V, Látalová K, Mareš J, Urbánek K, Herzig R, Bekárek V et al. Stanovení tau-proteinu a beta amyloidu jako možných diagnostických markerů demencí. Cesk Slov Neurol N 2004; 67/100(5): 330–334.

23. Nägga K, Gottfries J, Blennow K, Marcusson J. Cerebrospinal fluid phospho-tau, total tau and beta-amyloid (1-42) in the differentiation between Alzheimer’s disease and vascular dementia. Dement Geriatr Cogn Disord 2002; 14(4): 183–190.

24. Hu YY, He SS, Wang X, Duan QH, Grundke-Igbal I, Igbal K et al. Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients: an ultrasensitive bioenzyme- substrate-recycle enzyme linked immunosorbent assay. Am J Pathol 2002; 160(4): 1269–1278.

25. Sjögren M, Vanderstichele H, Agren H, Zachrisson O, Edsbagge M, Wikkelso C et al. Tau and Aß42 in cerebrospinal fluid from healthy adults 21–93 years of age: Establishment of reference values. Clin Chem 2001; 47(10): 1776–1781.

26. Otto M, Wiltfang J, Tumani H, Zerr I, Lantsch M, Kornhuber J et al. Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurosci Lett 1997; 225(3): 210–212.

27. Giraud P, Biacabe AG, Chazot G, Later R, Joyeux O, Moene Y et al. Increased detection of 14-3-3 protein in cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease during the disease course. Eur Neurol 2002; 48(4): 218–221.

28. Van Everbroeck B, Green A, Vanmechelen E, Vanderstichele H, Pals P, Sanchez-Valle R et al. Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 2002; 73(1): 79–81.